CA2069255C - Granules of .alpha.-l-aspartyl-l-phenylalanine methyl ester - Google Patents
Granules of .alpha.-l-aspartyl-l-phenylalanine methyl ester Download PDFInfo
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- CA2069255C CA2069255C CA002069255A CA2069255A CA2069255C CA 2069255 C CA2069255 C CA 2069255C CA 002069255 A CA002069255 A CA 002069255A CA 2069255 A CA2069255 A CA 2069255A CA 2069255 C CA2069255 C CA 2069255C
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- crystals
- granules
- apm
- grain size
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
- C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
- C07K5/0613—Aspartame
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Granules of .alpha.-L-aspartyl-L-phenylalanine methyl ester, containing IB crystals of the ester and having a grain size of from 100 to 1400 .nu.m, have improved water solubility. The method of obtaining these granules is also disclosed.
Description
~~~q2 ~5 The present invention relates to granules of_ a-L-aspartyl-L-phenylal.anine methyl ester (a-APM) having improved water solubility.
a -APM is a dipeptide sweetener having a sweetness of about 200 times that of sucrose (cane sugar). Because of its extreme sweetness and its low calory content, it is widely used as a diet sweetener, and the worldwide demand for it is estimated to be over 7.0,000 tons by 1995.
Since a-APM is a sweetener which has little bitterness or bad aftertaste, in contrast to other high sweetness sweeteners, it is widely used and known as a low calory sweetener. However, one drawback is often pointed out: its dispersibility and solubility in water is poor. Therefore, in order to obtain a-APM having excellent solubility, various investigations for granulating or foaming and tableting it have been made by adding a vehicle or desi.ntegrator thereto.
I-Iowever, i.ncorpo.ration of a vehicle into a-APM :is often problematic For specific uses.
Therefore, an a-APM of high purity and high solubility is greatly de sired.
In an attempt to improve 'the solubility of a-APM while maintai.n:ing its high purity, a method of spray-drying a slurry of a-APM has been disclosed (Japanese Patent Publication 58-20558). A method of granulating a-APM, to wh.i.ch water has been added to a specified water content is also known (Japanese Patent Application Laid-Open No. 59-95862).
~~~~2~~
On the other hand, processes for producing a-APM crystals to give various crystal Forms are also known (European Patent 0119~337 ) . Of these crystal forms, IB crystals have a higher solubility than IIA
crystals and IIB crystals, when considered as dry crystals.
However, the IB form of ~-APM crystals is known to still contain crystals having low solubility. For example, such crystal characteristics as bundle like crystal form or needl.elike crystal farm cause noticeable differences in the dispersibi.li.ty and solubility of crystals in water. Bundle like crystals have a higher dispersibility and solubility in water than needlelike crystals.
IB needlelike crystals often require a long time for dispersing or dissolving them into water, which almost comp tires to IIA crystals or IIB
crystals, depending upon the crystallization and drying conditions employed in preparing them.
The term "needl.el..ike cryst.al.s", referred to herein, indicate those crystals which are obtained by crystallization initiated by cooling under ordinary stirring conditions without formation of a pseudo solid phase.
The term "bundle like crystals", referred to herein with respect t.o crystal behavior, indicates those crystals which are obtained by crystallization under cooling o.f an ~Y-APM solution with no stirring via its pseudo solid phase, as described i.n Japanese Pat ent Publication No. 2-X5638 (crystallization of a-APM). V~lhen these crystals are observed with a 20692~~
scanning electron microscope (SEM) under magnification, they are found to be crystal aggregates in which a plurality of ne2dlelike crystals are bundled together to seemingly form one crystal.
An object of the present invention is to improve the solubility of the above mentioned IB
crystals of a-APM having a poor solubility, to such a degree that the time necessary for dissolving these crystals is half or less the time necessary for dissolving the original powder of the compound.
This and other objects, ~ which will become apparent in the following description of exemplary embodiments, have been achieved by the process according to the present invention, wherein the solubility of IB crystals of a -APM is improved by granulating the crystals to a grain size of 100-1400 microns.
It has now been discovered that the solubility of IB needlelike crystals of a-APM is improved by granulating the crystals to grains having a particular grain size.
A binder is used for granulating and shaping the a-APM crystals. One or more binders such as water and aqueous solutions of alcohols, saccharides and inorganic materials such as lactose, lactose anhydride, dextrin, gelatin, soluble starch, sucrose, sorbitol, etc. may be used as the binder.
The granulation of a-APM may be carried out by any known method of mixing granulation, powder compression granulation, extrusion granulation, 20692~~
fluidizing granulation, rolling granulation, pulverizing granulation and the like. From the view point of low heat load and for the purpose of avoiding complicated processing, dry granulation such as powder compression granulation is industrially preferred.
The magnitude of the effect of the present invention depends upon the content of IB crystal's in the granulated a-APM product. When the content of IB
crystals is large, the product must be granulated to a relatively narrow grain size range. However, when the content of IB crystals is low, the effect of the present invention takes place over a much broader grain size range.
The grain size of the granulated product containing a high amount of IH crystals, i.e. an amount of 90 wt.$ or more, must be within the range of from 100'to 500 um, preferably from 150 to 300 vm.
I~ the grain size is less than 100 um, the water dispersibility of the granules is poor and dissolution o~ the granules requires long periods of time. On the other hand, if the grain size is more than 500 um, the contact area between water and the granules is unfavorably decreased so that improvement of the water solubility of the granules can not be attained and the time necessary for dissolution in water can not be reduced to half or less that time necessary for dissolving the original powder of the compound.
Therefore, the preferred size of the granulated product is from 100 to 500 um. Where the size of the granulated product falls within this _4_ 20fi9~5~
range, the time necessary for dissolving the granulated low solubility IB crystals of «-APM in water is reduced to about half or less the time necessary for dissolving the original powder of the compound.
As used herein, the term "original powder"
means the a-APM which is used as the starting material for the present process, prior to granulation. Such starting original powders will generally have a size on the order of millimeters.
The original powder may be produced by cooling crystallization with or without stirring.
When the content of IB crystals is low, i.e. less than 10 wt.~ in the «~-APM to be granulated, the solubility of the original a-ApM powder itself is low. Therefore, the improvement in the solubility of the granulated product obtained from it is achieved over a broad range of grain sizes. That is, the grain size of the granulated product may be within the range of from 100 to 1400 gym, preferably trom 150 to 500 um. When the grain size is within this defined range, the time necessary for dissolving the granulated product in water is reduced to about half or less the time necessary for dissolving the original powder of the compound, i.e. a high purity a-APM product.
In accordance with the present invention, even low solubility powdered a-APM containing IB
crystals can be formed into granules having an improved solubility in water. When the granules of «-APM of the present invention are added to drink or other products, the time necessary for dissolving them is reduced and the distribution of the operation 20E~2~~
time for dissolution is also to be reduced. As a result, the granules of a-APM of the present invention may be handled with high efficiency.
Other features of the invention will become apparent in the course of the following description of exemplary embodiments which are given for illustrating the invention and are not intended to limit its scope.
Sample A:
Example A powder of a -APM was prepared in accordance with the method mentioned below as a sample for evaluation.
An aqueous a-APM solution was crystallized by ordinary cooling crystallization, while stirring the solution (stirring crystallization not forming a pseudo solid phase). By centrifugation, wet a-APM
crystals having a water content of 60 wt.$ were obtained, and were dried in a small fluidizing drier at 90°C for 30 minutes. Then, the wet crystals were milled in a small centrifugal mill (5000 rpm, using a 1 mm screen) to obtain an original IB needlelike crystal powder which was identified as sample A.
Sample B:
380 ml of an aqueous solution containing 1~.~ kg of a-APM dissolved therein (55°C, initial concentration of a-APM 4.4 wt.$) were placed in a cooling jacketed stainless steel crystallizer having a diameter of 400 mm and a cooling plate on the inside thereof. A coolant at 0°C was circulated ~0~92~~
through the cooling jacket and the cooling plate and the content in the crystallizer was cooled for 3 hours.
After about one hour, the entire solution became a pseudo solid phase. The pseudo solid phase containing a-APM crystals was dropped into a receiver provided with a cooling coil and a stirrer and pulverized therein to form a slurry, which was further cooled. Cooling was effected from 16°C to 7oC in the receiver.
The slurry thus obtained was filtered and dewatered in a centrifugal separator having a diameter of 36 inches to give wet a -APM crystals having a water content of 30 wt.~.
The wet a-APM crystals thus obtained by the pseudo solid phase method were dried in a small fluidizing drier at 90°C fox 30 minutes and then milled in a small centrifugal mill (5000 rpm, using a 1 mm screen) to give an original IB bundle like crystal powder which was identified as sample B.
Sample C:
An aqueous solution of a -APM was crystallized by ordinary cooling crystallization, whereupon the solution was stirred (stirring crystallization not forming a pseudo solid phase).
Wet a-APM.crystals having a water content of 60 wt.~
were obtained by centrifugation, and were continuously fed into a MICRON DRIER (manufactured by Hosokawa Micron Co.) via a screw feeder and were air dried therein with hot air at 140aC to give an original IIA needlelike crystal powder.
2U692~5 40 wt.~ of the thus obtained original IIA
needlelike crystal powder and 60 wt.~ of the previously obtained original IB needlelike crystal powder (sample A) were blended to give sample C.
Granulation:
Each of samples A, B and C were shaped by compression shaping to give compressed flakes, which were then pulverized in a fine granulator and sieved through JTS standard sieves to obtain several groups of a-APM granules each having the grain size range shown in Table 1 below.
Dry compression shaping followed by pulverizing was conducted using a ROLLER COMPACTOR
model WP90 X 30 (manufactured by Turbo Industrial Co.). The feed rate of the original powder during compression shaping step was 40 g/min, the roll pressure was 50kg/cm2.G and the roll rotating speed was 12 rpm: The screen of the fine granulator as used in the pulverizing step had a 12-mesh screen (with opening of 1400 um).
The dissolution time of the a-APM granules thus obtained was measured by the method described below. The results obtained are shown in Table 1.
Dissolution time:
Two liters of water where placed in a 3-liter beaker and stirred with a magnetic stirrer.
The size of the stirrer used for stirring was 70 mm x 15 mm and the rotation sped was set at 350 rpm using a Whatman DATAPLATE 440. The water temperature was maintained at 20°C using a hot plate. 8 g of each _g_ sample were introduced into the water under these conditions, and the time required for complete dissolution in the water was measured.
Dissolution Time (min) Grain Size ~
(~'n") A B C
850 to 140038 ' ' 35 . 38 500 to 850 25 24 27 300 to 500 18 17 19 180 to 300 11 9 12 150 to 180 8 7 - 20 100 to 150 15 10 36 (Original 30 15 60 , Powder before Granulation) z5 Obviously, numerous modifications and variations of the present invention are possible in 30 the light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.
a -APM is a dipeptide sweetener having a sweetness of about 200 times that of sucrose (cane sugar). Because of its extreme sweetness and its low calory content, it is widely used as a diet sweetener, and the worldwide demand for it is estimated to be over 7.0,000 tons by 1995.
Since a-APM is a sweetener which has little bitterness or bad aftertaste, in contrast to other high sweetness sweeteners, it is widely used and known as a low calory sweetener. However, one drawback is often pointed out: its dispersibility and solubility in water is poor. Therefore, in order to obtain a-APM having excellent solubility, various investigations for granulating or foaming and tableting it have been made by adding a vehicle or desi.ntegrator thereto.
I-Iowever, i.ncorpo.ration of a vehicle into a-APM :is often problematic For specific uses.
Therefore, an a-APM of high purity and high solubility is greatly de sired.
In an attempt to improve 'the solubility of a-APM while maintai.n:ing its high purity, a method of spray-drying a slurry of a-APM has been disclosed (Japanese Patent Publication 58-20558). A method of granulating a-APM, to wh.i.ch water has been added to a specified water content is also known (Japanese Patent Application Laid-Open No. 59-95862).
~~~~2~~
On the other hand, processes for producing a-APM crystals to give various crystal Forms are also known (European Patent 0119~337 ) . Of these crystal forms, IB crystals have a higher solubility than IIA
crystals and IIB crystals, when considered as dry crystals.
However, the IB form of ~-APM crystals is known to still contain crystals having low solubility. For example, such crystal characteristics as bundle like crystal form or needl.elike crystal farm cause noticeable differences in the dispersibi.li.ty and solubility of crystals in water. Bundle like crystals have a higher dispersibility and solubility in water than needlelike crystals.
IB needlelike crystals often require a long time for dispersing or dissolving them into water, which almost comp tires to IIA crystals or IIB
crystals, depending upon the crystallization and drying conditions employed in preparing them.
The term "needl.el..ike cryst.al.s", referred to herein, indicate those crystals which are obtained by crystallization initiated by cooling under ordinary stirring conditions without formation of a pseudo solid phase.
The term "bundle like crystals", referred to herein with respect t.o crystal behavior, indicates those crystals which are obtained by crystallization under cooling o.f an ~Y-APM solution with no stirring via its pseudo solid phase, as described i.n Japanese Pat ent Publication No. 2-X5638 (crystallization of a-APM). V~lhen these crystals are observed with a 20692~~
scanning electron microscope (SEM) under magnification, they are found to be crystal aggregates in which a plurality of ne2dlelike crystals are bundled together to seemingly form one crystal.
An object of the present invention is to improve the solubility of the above mentioned IB
crystals of a-APM having a poor solubility, to such a degree that the time necessary for dissolving these crystals is half or less the time necessary for dissolving the original powder of the compound.
This and other objects, ~ which will become apparent in the following description of exemplary embodiments, have been achieved by the process according to the present invention, wherein the solubility of IB crystals of a -APM is improved by granulating the crystals to a grain size of 100-1400 microns.
It has now been discovered that the solubility of IB needlelike crystals of a-APM is improved by granulating the crystals to grains having a particular grain size.
A binder is used for granulating and shaping the a-APM crystals. One or more binders such as water and aqueous solutions of alcohols, saccharides and inorganic materials such as lactose, lactose anhydride, dextrin, gelatin, soluble starch, sucrose, sorbitol, etc. may be used as the binder.
The granulation of a-APM may be carried out by any known method of mixing granulation, powder compression granulation, extrusion granulation, 20692~~
fluidizing granulation, rolling granulation, pulverizing granulation and the like. From the view point of low heat load and for the purpose of avoiding complicated processing, dry granulation such as powder compression granulation is industrially preferred.
The magnitude of the effect of the present invention depends upon the content of IB crystal's in the granulated a-APM product. When the content of IB
crystals is large, the product must be granulated to a relatively narrow grain size range. However, when the content of IB crystals is low, the effect of the present invention takes place over a much broader grain size range.
The grain size of the granulated product containing a high amount of IH crystals, i.e. an amount of 90 wt.$ or more, must be within the range of from 100'to 500 um, preferably from 150 to 300 vm.
I~ the grain size is less than 100 um, the water dispersibility of the granules is poor and dissolution o~ the granules requires long periods of time. On the other hand, if the grain size is more than 500 um, the contact area between water and the granules is unfavorably decreased so that improvement of the water solubility of the granules can not be attained and the time necessary for dissolution in water can not be reduced to half or less that time necessary for dissolving the original powder of the compound.
Therefore, the preferred size of the granulated product is from 100 to 500 um. Where the size of the granulated product falls within this _4_ 20fi9~5~
range, the time necessary for dissolving the granulated low solubility IB crystals of «-APM in water is reduced to about half or less the time necessary for dissolving the original powder of the compound.
As used herein, the term "original powder"
means the a-APM which is used as the starting material for the present process, prior to granulation. Such starting original powders will generally have a size on the order of millimeters.
The original powder may be produced by cooling crystallization with or without stirring.
When the content of IB crystals is low, i.e. less than 10 wt.~ in the «~-APM to be granulated, the solubility of the original a-ApM powder itself is low. Therefore, the improvement in the solubility of the granulated product obtained from it is achieved over a broad range of grain sizes. That is, the grain size of the granulated product may be within the range of from 100 to 1400 gym, preferably trom 150 to 500 um. When the grain size is within this defined range, the time necessary for dissolving the granulated product in water is reduced to about half or less the time necessary for dissolving the original powder of the compound, i.e. a high purity a-APM product.
In accordance with the present invention, even low solubility powdered a-APM containing IB
crystals can be formed into granules having an improved solubility in water. When the granules of «-APM of the present invention are added to drink or other products, the time necessary for dissolving them is reduced and the distribution of the operation 20E~2~~
time for dissolution is also to be reduced. As a result, the granules of a-APM of the present invention may be handled with high efficiency.
Other features of the invention will become apparent in the course of the following description of exemplary embodiments which are given for illustrating the invention and are not intended to limit its scope.
Sample A:
Example A powder of a -APM was prepared in accordance with the method mentioned below as a sample for evaluation.
An aqueous a-APM solution was crystallized by ordinary cooling crystallization, while stirring the solution (stirring crystallization not forming a pseudo solid phase). By centrifugation, wet a-APM
crystals having a water content of 60 wt.$ were obtained, and were dried in a small fluidizing drier at 90°C for 30 minutes. Then, the wet crystals were milled in a small centrifugal mill (5000 rpm, using a 1 mm screen) to obtain an original IB needlelike crystal powder which was identified as sample A.
Sample B:
380 ml of an aqueous solution containing 1~.~ kg of a-APM dissolved therein (55°C, initial concentration of a-APM 4.4 wt.$) were placed in a cooling jacketed stainless steel crystallizer having a diameter of 400 mm and a cooling plate on the inside thereof. A coolant at 0°C was circulated ~0~92~~
through the cooling jacket and the cooling plate and the content in the crystallizer was cooled for 3 hours.
After about one hour, the entire solution became a pseudo solid phase. The pseudo solid phase containing a-APM crystals was dropped into a receiver provided with a cooling coil and a stirrer and pulverized therein to form a slurry, which was further cooled. Cooling was effected from 16°C to 7oC in the receiver.
The slurry thus obtained was filtered and dewatered in a centrifugal separator having a diameter of 36 inches to give wet a -APM crystals having a water content of 30 wt.~.
The wet a-APM crystals thus obtained by the pseudo solid phase method were dried in a small fluidizing drier at 90°C fox 30 minutes and then milled in a small centrifugal mill (5000 rpm, using a 1 mm screen) to give an original IB bundle like crystal powder which was identified as sample B.
Sample C:
An aqueous solution of a -APM was crystallized by ordinary cooling crystallization, whereupon the solution was stirred (stirring crystallization not forming a pseudo solid phase).
Wet a-APM.crystals having a water content of 60 wt.~
were obtained by centrifugation, and were continuously fed into a MICRON DRIER (manufactured by Hosokawa Micron Co.) via a screw feeder and were air dried therein with hot air at 140aC to give an original IIA needlelike crystal powder.
2U692~5 40 wt.~ of the thus obtained original IIA
needlelike crystal powder and 60 wt.~ of the previously obtained original IB needlelike crystal powder (sample A) were blended to give sample C.
Granulation:
Each of samples A, B and C were shaped by compression shaping to give compressed flakes, which were then pulverized in a fine granulator and sieved through JTS standard sieves to obtain several groups of a-APM granules each having the grain size range shown in Table 1 below.
Dry compression shaping followed by pulverizing was conducted using a ROLLER COMPACTOR
model WP90 X 30 (manufactured by Turbo Industrial Co.). The feed rate of the original powder during compression shaping step was 40 g/min, the roll pressure was 50kg/cm2.G and the roll rotating speed was 12 rpm: The screen of the fine granulator as used in the pulverizing step had a 12-mesh screen (with opening of 1400 um).
The dissolution time of the a-APM granules thus obtained was measured by the method described below. The results obtained are shown in Table 1.
Dissolution time:
Two liters of water where placed in a 3-liter beaker and stirred with a magnetic stirrer.
The size of the stirrer used for stirring was 70 mm x 15 mm and the rotation sped was set at 350 rpm using a Whatman DATAPLATE 440. The water temperature was maintained at 20°C using a hot plate. 8 g of each _g_ sample were introduced into the water under these conditions, and the time required for complete dissolution in the water was measured.
Dissolution Time (min) Grain Size ~
(~'n") A B C
850 to 140038 ' ' 35 . 38 500 to 850 25 24 27 300 to 500 18 17 19 180 to 300 11 9 12 150 to 180 8 7 - 20 100 to 150 15 10 36 (Original 30 15 60 , Powder before Granulation) z5 Obviously, numerous modifications and variations of the present invention are possible in 30 the light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.
Claims (11)
1. Granules of .alpha.-L-aspartyl-L-phenylalanine methyl ester containing IB crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester and having a grain size within the range of 100 to 1400 .nu.m.
2. The granules of claim 1, having a grain size within the range of 150 to 500 .nu.m.
3. The granules of claim 1, containing at least 90 wt. % of said IB crystals and having a grain size within the range of 100 to 500 .nu.m.
4. The granules of claim 3, having a grain size within the range of 150 to 300 .nu.m.
5. The granules of claim 1, containing less than 10 wt.% of said IB crystals and having a grain size within the range of 100 to 500 .nu.m.
6. The granules of claim 1, wherein said granules dissolve in water within a period of time which is half or less than the time required for dissolving a powder of .alpha.-APM produced by cooling crystallization of .alpha.-APM.
7. A method of improving the water solubility of .alpha.-L-aspartyl-L-phenylalanine methyl ester crystals containing IB crystals of said ester obtained by cooling crystallization of said ester with or without stirring, comprising granulating said .alpha.-L-aspartyl-L-phenylalanine methyl ester crystals to a grain size falling within the range of 100 to 1400 .nu.m.
8. The method of claim 7, wherein said ester crystals are granulated to a grain size within the range of 150 to 500 .nu.m.
9. The method of claim 7, wherein said ester crystals contain at least 90 wt.% of said IB crystals and comprising granulating said ester crystals to a grain size within the range of 100 to 500 .nu.m.
10. The method of claim 9, comprising granulating said ester crystals to a grain size within the range of 150 to 300 .nu.m.
11. The method of claim 7, wherein said ester crystals contain less than 10 wt.% of said IB
crystals and comprising granulating said ester crystals to a grain size within the range of 150 to 500 .nu.m.
crystals and comprising granulating said ester crystals to a grain size within the range of 150 to 500 .nu.m.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP222525/1991 | 1991-05-24 | ||
| JP3222525A JP3019519B2 (en) | 1991-05-24 | 1991-05-24 | α-L-aspartyl-L-phenylalanine methyl ester granules |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2069255A1 CA2069255A1 (en) | 1992-11-25 |
| CA2069255C true CA2069255C (en) | 2002-07-23 |
Family
ID=16783800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002069255A Expired - Lifetime CA2069255C (en) | 1991-05-24 | 1992-05-22 | Granules of .alpha.-l-aspartyl-l-phenylalanine methyl ester |
Country Status (4)
| Country | Link |
|---|---|
| EP (2) | EP0514937B1 (en) |
| JP (1) | JP3019519B2 (en) |
| CA (1) | CA2069255C (en) |
| DE (2) | DE69232249T2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3648959B2 (en) * | 1997-12-22 | 2005-05-18 | 味の素株式会社 | Sweetener composition |
| JP3646497B2 (en) * | 1997-12-22 | 2005-05-11 | 味の素株式会社 | Granular sweetener |
| JPH11322788A (en) * | 1998-05-08 | 1999-11-24 | Ajinomoto Co Inc | New aspartame derivative crystal and its production |
| JP2000026496A (en) * | 1998-05-08 | 2000-01-25 | Ajinomoto Co Inc | New aspartame derivative crystal and its production |
| US9101160B2 (en) | 2005-11-23 | 2015-08-11 | The Coca-Cola Company | Condiments with high-potency sweetener |
| US8017168B2 (en) | 2006-11-02 | 2011-09-13 | The Coca-Cola Company | High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0710878B2 (en) * | 1986-07-28 | 1995-02-08 | 東ソー株式会社 | Process for producing α-L-aspartyl-L-phenylalanine methyl ester with improved solubility |
| EP0362706B1 (en) * | 1988-10-03 | 1996-01-17 | Ajinomoto Co., Inc. | Process for preparing dry IB type crystals of alpha-L-aspartyl-L-phenylalanine methyl ester having improved solubility |
| JP2756571B2 (en) * | 1988-12-26 | 1998-05-25 | 東ソー株式会社 | Method for producing granular dipeptide sweetener |
| US5043169A (en) * | 1990-05-25 | 1991-08-27 | Warner-Lambert Company | Stabilized Sweetner Composition |
-
1991
- 1991-05-24 JP JP3222525A patent/JP3019519B2/en not_active Expired - Lifetime
-
1992
- 1992-05-22 CA CA002069255A patent/CA2069255C/en not_active Expired - Lifetime
- 1992-05-22 DE DE69232249T patent/DE69232249T2/en not_active Expired - Lifetime
- 1992-05-22 EP EP92108705A patent/EP0514937B1/en not_active Expired - Lifetime
- 1992-05-22 EP EP00119187A patent/EP1067137B1/en not_active Expired - Lifetime
- 1992-05-22 DE DE69233764T patent/DE69233764D1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2069255A1 (en) | 1992-11-25 |
| EP1067137A3 (en) | 2001-05-16 |
| EP0514937A1 (en) | 1992-11-25 |
| DE69233764D1 (en) | 2009-08-27 |
| DE69232249T2 (en) | 2002-08-22 |
| DE69232249D1 (en) | 2002-01-17 |
| JPH04346769A (en) | 1992-12-02 |
| EP1067137A2 (en) | 2001-01-10 |
| JP3019519B2 (en) | 2000-03-13 |
| EP1067137B1 (en) | 2009-07-15 |
| EP0514937B1 (en) | 2001-12-05 |
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